In somewhat of a strange bedfellows situation, both PhRMA and GPhA support a proposed alternative to the FDA proposed labeling Rule (see previous posts here, here, here, here, here, here, here, here, and here) called the “Expedited Agency Review” (EAR) for safety label changes.

The two industry groups argue that only the FDA has all of the information to make an accurate and informed judgement as to proposed safety label changes.  For instance, FDA is the repository for all clinical trial data, as well as the adverse event reporting from all applicants (NDA and ANDA holder).  FDA is thus in the best position to evaluate the totality of data to make a determination that any “new safety information” would rise to the level where a label change would be necessary.  Individual applicants only see a fraction of the adverse event reporting and FDA also has full access to the Sentinel System that “will allow FDA to identify an increased risk of common events that healthcare providers may not suspect are related to medical products.  Therefore, public health can be protected more effectively by using the Sentinel System and relying far less on the historical passive reporting processes.”

The EAR plan will require that FDA evaluate reports of safety data submitted by an NDA or ANDA applicant and make a determination as to whether that data constitutes “new safety” data that would warrant a label change.  The FDA would have a set timeframe to make that decision, would then notify all applicants that a change must be made, and establish a timeframe for revision of the label of 30 days or sooner if the situation warrants.  In this manner, then, FDA would review and approve the changes submitted by an NDA or ANDA holder, thus permitting ANDA applicants to use a process that is currently in existence (i.e., to notify the Agency of a potential issue), but it would be the FDA that decides whether the information rises to the level of requiring a label change.  This would ensure the sameness of labeling provisions of the Hatch-Waxman Act are preserved (and consistent with the Supreme Court decision in the Mensing case), while at the same time provide required well-documented safety information to all consumers in a consistent manner, and would eliminate the potential for significant labeling differences, some of which may not actually be supported by the data, among the same product.

Rapid dissemination of “new safety” information determined to be appropriate for label changes can be facilitated by e-labeling, which is the goal of the current FDA proposed Rule.   The GPhA/PhRMA process is fairly simple and straightforward and will eliminate confusion in the marketplace that would occur with the potential for multiple different labeling of the same product should the FDA Rule publish as currently written.

The process is outlined by the groups to look like this:

Step 1.  NDA or ANDA holder requests EAR or FDA initiates EAR on its own.

Step 2.  FDA begins review of all available safety data and engages NDA and ANDA holders in discussion of potential label change.

Step 3.  If FDA determines (through a review of all available safety data) that a labeling change is required, FDA informs the NDA and ANDA holders of the content of the final labeling language immediately (within 15 days) and instructs the NDA and ANDA holders to update their labeling within 30 days via e-labeling.

Step 4.  All application holders update labeling via e-labeling within 30 days.

While this will put a greater burden on the FDA, they are the only party that has access to all of the data necessary to accurately evaluate the need for a label revision.  The full views of the organizations will be presented at the March 27, 2015 FDA public meeting.